Localization-guided surgery for breast cancer.

The importance of localizationguided surgery in breast cancer cannot be underestimated. In countries with screening programmes, one-third of all breast cancers diagnosed are clinically occult1. The extension of breast screening age and increased utilization of advanced imaging modalities such as MRI mean that localization-guided surgery will become increasingly necessary. The standard technique, used since the onset of screening mammography, is wire-guided localization (WGL) surgery. Outcomes vary, with re-excision (second operation) rates of up to 40 per cent2 as well as technical and logistical limitations3,4. These drawbacks have resulted in the development of alternative localization techniques, of which the most widely reported have been radio-guided localization (RGL) and intraoperative ultrasonography (IOUS). Despite being described over 15 years ago and reported in cohort series of more than 1000 patients, with re-excision rates below 10 per cent, neither of the two radio-guided techniques – radio-guided occult lesion localization and radioactive seed localization – has been widely adopted5,6. The latest meta-analysis of RGL versus WGL4 demonstrated that RGL provided a significantly shorter operating time but with a significantly larger volume of excised tissue. The seven randomized clinical trials (RCTs) in this meta-analysis had inherent methodological limitations, with one carrying 85 per cent weight in the meta-analysis for volume of specimens excised. Only three trials had prespecified power calculations on sample size. These calculations grossly overestimated the difference in involved margin rates between the two techniques. The anticipated 15–20 per cent difference in involved margin rates was found to be less than 7 per cent when the studies were completed. Although the only meta-analysis of IOUS versus WGL3 identified a reduced involved margin rate for IOUS, it included a solitary RCT and nine observational studies, making strong recommendation impossible. Legislative issues associated with handling and disposal of radioisotopes may have affected the uptake of RGL. Although licensing is usually required for the clinical use of radiation, this can simply be an extension of any existing licence used for sentinel lymph node biopsy, as the use of radioisotopes combined with blue dye is the current standard of care7. Establishing such a programme should not be difficult, therefore, for most institutions. Localization based on IOUS may be more difficult to establish, where a clear limitation exists regarding the ability of surgeons to gain adequate experience in breast ultrasound imaging8. Despite training courses, maintaining and documenting experience has resulted in a low uptake among surgeons8. Other techniques such as magnetic localization9 are in development stages. With uptake of the current ‘established’ alternatives to WGL being so poor, there is a risk that additional novel techniques will also remain confined to centres with a research interest, again failing to change clinical practice away from WGL. In an era of rapid advances in technology that allows surgeons to be guided by miniaturized visualization techniques, the use of two-view mammography seems both crude and outdated. As the next generation of surgeons becomes increasingly familiar with technology and finds it more intuitive to localize targets, the dominance of the wire is likely to diminish. For the patient, the potential benefits of alternative techniques need to be readily available rather than remain with a few enthusiasts. The only way to prevent the latter is to ensure that novel techniques are assessed rigorously to enable a change in clinical practice. Once proof of principle, safety and feasibility have been demonstrated, multicentre studies should be initiated to gain a realistic assessment of key outcome measures, such as generalizability of re-excision rates (currently running at 20 per cent in the UK10). From the experience of RGL, it is clear, in the context of RCTs, that expecting a 15–20 per cent difference between techniques for re-excision rates is unrealistic, and a smaller difference of 10 per cent would seem more reasonable. Rigorous assessment of alternative localization techniques means that any possessing merit will be actually adopted in clinical practice. This will avoid the current scenario where believers in current alternatives such as RGL and IOUS continue to use them with excellent cancer-related outcomes, while the rest of the surgical community refer to the lack of robust evidence as justification not to move away from the established wire.